I've realized, after re-reading your post a few times that you meant a Cisco IPS 4255. I'm not entirely sure that you can block skype specifically as it uses 80 and 443. If you can it's because they have a protocol built in for it. There are some built already for kazaa, limewire, etc... the other method would be to do an explicit deny using a url filter for skype.com. I believe all the connections have to go through there. In the future please try and give more information in your initial posts.

The Skype application was coded not to be port or IP specific with regard to destination. To make the problem more difficult - communication between Skype clients and Skype servers are encrypted by the application. It's still uses https as it's protocol, so there is no way too catch those streams without becoming the "man in the middle" via proxy or IOS NBAR. You'll have a difficult time catching a signature you can pass on to and IPS or ASA.

Skype can be limited by implementing; CSA / CSD on the client - limiting the applications rights to run or even be installed, or via a corporate IT policy if something like that is available in your organization.

Messengers of various flavors (not all are coded equally) can be signature blocked by ASA and I'm sure via the IPS 4255 as well. I've located a few articles across the web with how-to's for different devices. Most mainstream messaging clients (MSN, Yahoo!, and GTalk for example) have distinct and known signatures that application inspection can catch, identify and subsequently block. Some messaging clients have options to port forward in order to circumvent proxies and thus network security.

I'm sure this wasn't the exact answer you were looking for - unfortunately in some cases the problem is easier to attack at the source (client desktop) than on the network.